Proteoglycans are a diverse group of proteins that carry a sulfated carbohydrate component, glycosaminoglycan, attached to a core protein. There are four main types of glycosaminoglycan: heparin/heparan sulfate, chondroitin sulfate/dermatan sulfate, keratan sulfate and hyaluronic acid. The core proteins of proteoglycans vary in size from 1,000 to more than 200,000 daltons and the number of glycosaminoglycan chains attached to the core varies from one to about 100. In addition, some proteoglycans also contain N-linked and O-linked oligosaccharides.
Proteoglycans are functionally as well as structurally heterogeneous. Currently, their known or proposed functions include a space-filling or structural role in tissues or at tissue boundaries, regulation of receptor function, regulation of growth and differentiation, regulation of proteinase activities and modulation of cell adhesion.
Large aggregating proteoglycans that carry primarily chondroitin sulfate side chains are present in the extracellular matrix of a wide variety of tissues including cartilage, skin, tendon and placenta. It is likely that these large proteoglycans play a role in cell-extracellular matrix interactions, since their core proteins bind to hyaluronic acid and contain potential binding sites for other molecules.
Some core proteins of proteoglycans contain domains with homologies to various binding elements. For example, the growth-factor-like domains may function in the transmission of regulatory signals to cells and lectin-like domains may bind to oligosaccharides of interstitial collagens. Moreover, one identified proteoglycan domain binds to hyaluronic acid.
Hyaluronic acid is a carbohydrate composed of a repeated sequence of glucuronic acid and Nacetylglucosamine units. Hyaluronic acid appears to play a role in the migration of cells through tissues, such as occurs in development and wound healing. Its presence attracts water, thereby causing swelling of the matrix. It is used as both a tissue substitute and lubricant in wound healing and treatment of joint diseases
Because of the importance of proteoglycans in cell function and metabolism, there is a need for additional proteoglycans, particularly those which can interact with hyaluronic acid. The present invention satisfies this need, and provides related advantages as well.